The scope of this Core is to provide unique and innovative capabilities for the design and highaffinity, selective and drug-like compounds against the proposed targets. Bridging several disciplines within our NCDDG program, and collaborating closely with Projects 1 to 4 and the Chemistry Core, we will bring unique capabilities to the lead identification and optimization processes by combining structure-based design and our innovative NMR-based techniques, The specific tasks can be summarized as follows: 1) to provide support to Projects 1 to 4 in the identification of lead compounds by using molecular modeling and NMR-based techniques;2) to provide support to Projects 1 to 4, in close collaboration with the Chemistry Core, to design optimized, high-affinity, selective and drug-like compounds by using a combination of molecular modeling and NMR-based straegies. Given our demonstrated experience with the proposed approaches and the synergy with Projects 1 to 4 and the Chemistry Core, we are confident that our efforts wil result in the identification of several lead compounds for all the proposed targets.